scaled up process directly

Reactions and Separations

CEP November 2004 www.cepmagazine.org 37

MANY COSTLY AND TIME-CONSUMING startup problems can be avoided if key scaleupissues are understood and resolved during thedevelopment of a new chemical process. Processes areoften scaled up in stages from the lab to the pilot plant orsemi-works scale to obtain engineering data for commer-cial plant design. However, this staged scaleup strategy isnot always practical for specialty chemicals, which areoften characterized by multi-step batch syntheses and rela-tively low volume, and where speed to market and rapidramp-up are essential for commercial success.

This article explains how a direct scaleup strategy can beused to successfully move a new process directly from thebench to the commercial scale without demonstration in apilot plant. This approach involves conducting process devel-opment research in 18-L, geometrically similar mini-plants,with a focus on simulating expected manufacturing condi-tions and testing the operating boundaries. It emphasizesunderstanding particle processing, heat management, agita-tion, trace chemistry and other scale-sensitive issues.

Choosing a scaleup strategyScaleup is defined as The successful startup and oper-

ation of a commercial size unit whose design and operat-ing procedures are in part based upon experimentation anddemonstration at a smaller scale of operation (1). Manyfactors must be considered when selecting the scaleupstrategy. Answering a few process-specific and business-related questions early is key to a successful startup.

Process factors What are the critical factors of the new chemistry

and process? Are extreme temperatures, pressures orother conditions required? Are operating instructionscomplicated?

Does the process involve a single reaction, or is it amulti-step synthesis? If the last step in a multi-stepprocess will be piloted, will it be necessary to also makeintermediates at the pilot-plant scale, or are they commer-cially available?

Are new chemical technologies, unit operations orequipment being considered?

How novel is the new process? Have similar reactionsor processing steps been successfully scaled up?

Will the new process be run in batch, semi-batch orcontinuous mode?

Business factors Does the commercial success of the project depend on

a flawless initial production campaign? Is there an alternative supply of material in case start-

up problems limit the production rate? Are project economics sensitive to yield or to the abil-

ity to recover and recycle some of the streams at relativelyhigh levels?

What is the commercial timeline? Is there enoughtime to design, build and operate a pilot plant to gener-ate scaleup data and still meet the planned commerciallaunch?

From Bench to Plant:

Scale Up Specialty ChemicalProcesses Directly

RRoonnaalldd BB.. LLeennggThe Dow Chemical Co.

Many new chemical, particularly batch operations,can be scaled up directly from the bench to theplant by developing the process and performinglab testing with the scaleup in mind.

38 www.cepmagazine.org November 2004 CEP

If the startup is delayed, what is the impact on theproduct launch strategy and project economics?

Are significant quantities needed for the launch of theproduct, or will it be introduced into the market slowly?

Are development samples needed over a period oftime leading up to the launch?

If a pilot-plant campaign is being considered, will thebusiness support the cost and human resources needed toperform this activity?

Benefits and risksDirect scaleup avoids the costs for pilot-plant design,

construction and operation. Fewer resources are needed todevelop the process entirely at the bench scale.Development timelines can be compressed by eliminatingthe pilot-plant stage.

However, surprises that dont appear until the largerscale can be costly. More resources may be needed duringthe startup phase. The physical form, purity or perform-ance of the product may change as the process movesfrom the lab to the plant. Certain scale-sensitive parame-ters cannot be fully tested at the lab scale.

If these risks are unacceptable, it is good to realize thisearly so they can be addressed. A vital goal of processdevelopment, either at the bench or pilot scale, should beto understand the fundamentals prior to scaleup.

Scaleup issuesSome of the most common and difficult types of prob-

lems encountered during scaleup are particle formationand isolation, liquid/liquid separation, agitation, heat histo-ry and trace impurities. (Reaction scaleup is widely dis-cussed in the literature and will not be covered here, and itis assumed that a sound chemical route has already beenselected.) Often, scaleup problems are a combination ofseveral of these factors (2).

Particle formation and isolationSolids can form as a result of precipitation, often duirng

a reaction, or be produced intentionally, such as by crystal-lization. Generally, the goal is to form large, uniform parti-cles, which will be filtered, washed and dried more effi-ciently, and are of higher purity, than fine particles. Inalmost all cases, understanding and controlling the particlegrowth environment will result in better particles (3).

Many reactions are run in a semi-batch or continuous-addition mode, where one of the reactants is metered intothe reactor and the product formed is a solid. The order ofaddition, rate of addition and feed location, as well as theintensity and design of the agitation system, can all affectthe particle formation process. It is also important to con-

sider the physical aspects in addition to the chemicalaspects of the reaction, and how these affect the particlegrowth environment.

Crystallization processes involve creating a state ofsupersaturation, typically by cooling, evaporation, chemi-cal reaction or anti-solvent addition, which drives nucle-ation and particle growth. These processes are governedby the conditions of the environment immediately next tothe particle. A basic understanding of the solubility curveand supersaturation limit is quite helpful. Changing thesolvent phase composition can have a significant effect onthe solubility curve. Tools such as Fourier transforminfrared (FTIR) spectroscopy, optical density probes, andmicroscopes are very useful for studying and optimizingcrystallization processes. It is a good idea to determine thecrystal size distribution (CSD), shape, strength andwhether multiple polymorphs exist. The latter is particu-larly important in the pharmaceutical industry.

Particles are usually isolated in the lab by filtration.Scaleup to a pressure or vacuum filter can be predicted rea-sonably well from lab data (4). Vertical basket centrifugesare often used in batch fine-chemical plants; scaleup predic-tion for these is more difficult because they use centrifugalforce to deliquor the crystals. A specialized test using a fil-ter bucket centrifuge can be used to obtain scaleup data (5).Data can also be obtained from a 12-in.-dia. test unit, but upto 20 L of slurry may be required for one set of runs.Comparison of lab filtration performance for a new applica-tion and a similar one currently operating in a plant cen-trifuge can be helpful. If particles are sensitive to attrition,this should be incorporated into the design of the slurrytransfer equipment. Measuring the filtration rate as a func-tion of cake depth is very useful for estimating filtrationcycle times, which can be the rate-limiting step in the plant.

Cake washing evaluations should also be included in thelab experimental plan. Often, wash ratios in the plant are sig-nificantly higher than expected, which leads to higher costsand waste disposal challenges. Wash media can be introducedeither as a flood or a surface spray, so both should be evaluat-ed. If the cake has a tendency to crack and cause wash chan-neling, maintaining a liquid pool above the surface of thecake is desirable. Feed maldistribution, particularly on a cen-trifuge, can have a detrimental effect on wash effectiveness.Online filtrate conductivity can provide a relative indicationof the impurity level in the wash liquor, and can be used tooptimize the wash procedure.

If the solid is to be isolated as a dry product, dryingdata should be obtained. Larger particles tend to dry fasterand more completely. A thorough understanding of thethermal stability of the product to be dried is essential.Knowing the dust explosion potential and toxicity of the



solid is also extremely important. Some solids go througha viscous, pasty phase that can damage the dryers driveunit if it is not designed to handle the added powerrequirement. Finally, quality and toxicity should be con-sidered in the design of the packaging system.

Example 1: Switching the order of reagent additionimproves particle characteristics. A two-step, reactive precipi-tation illustrates the significance of reagent addition order:

R-Na+ + H+ R-H2R-H + 0.5 H2O2 R-R

First, acetic acid was added rapidly to a sodium-organicsalt in a 1,000-gal agitated reactor. This was followed by a1-h metered addition of hydrogen peroxide to form theproduct. The resulting product R-R particles were very fineand had poor centrifugation and washing performance.

A follow-up solubility study showed that the concentra-tion of R-H at the end of the acid addition exceeded thesolubility limit by a factor of three. When the supersaturat-ed R-H crashed out of solution, it was impossible to formlarge R-R particles.

The reagent-addition scheme was modified so the Na-Rsolution was added simultaneously with the peroxide intoa 2-gal lab reactor containing the acid and solvent. Theresulting particles were large (50100 mm) sphericalagglomerates with much improved filtration and washingcharacteristics (Figure 1). This modified approach wassuccessfully implemented in the plant.

Liquid/liquid systemsTwo aspects of scaling up multi-phase reactions and

solute extractions are: if you dont see an emulsion in the lab, you will

likely see one in the plant if you see an emulsion in the lab, it will likely be

worse in the plant.Process research should be focused on understanding

the cause and developing a method to prevent or breakthe emulsion.

For coalescence, and thus phase separation, to occur,small droplets of the dispersed phase must get closeenough to each other that the liquid continuous phasebetween the drops drains, allowing the drops to unite.Viscosity and surface tension are important variablesaffecting the coalescence rate.

It is useful to test the sensitivity of the phase separation toa variety of factors that simulate expected plant conditions,including the expected agitation intensity and the vesselsmaterials of construction. Agitator tip speed will normally behigher in the plant, which can lead to smaller drop size andslower coalescence rates. Sometimes corrosion salts, even atrelatively low levels, can impede the coalescence rate of tinydrops. Reagent or reaction impurities can accumulate at theliquid interface and reduce surface tension or prevent dropsfrom getting close enough to coalesce. Look for impuritiesthat have both hydrophilic and hydrophobic characteristics,which are attracted to both phases.

Even an empirical understanding of factors that improveor retard coalescence is helpful. Density difference is a keyvariable in gravity or centrifugal separation. If it is muchless than 0.1 specific gravity units, the difference may beincreased by changing the temperature, changing the sol-vent, or adding salt to the aqueous layer. The density of theorganic phase will usually decrease more with an increasein temperature than will the aqueous phase density.Adjusting the pH of the system may be beneficial.Changing the phase ratio can affect which is the dispersedphase and which is the continuous phase. Testing extremesto determine whether phase inversion can occur is wise.Consider whether the two-phase mixture will be subject toadditional shear, such as through a recirculation pump andloop. Often solid impurities can cause emulsions. Passingthe mixture through a syringe filter is a simple test that canusually identify if solids are part of the problem.Evaluation of interface detection methods, such as conduc-

tivity, capacitance or density, is usefulfor plant design. Examination of anemulsion under a microscope mayreveal causes of emulsions, such assolids or phase inversions.

Before scaling up, decide on aprocess strategy to deal with emul-sions. Processing methods can be eitherequipment- or process-related. If thereis a small density gradient between thephases, a decanting centrifuge can beused. If gravity settling is to beemployed, make sure to account for the Figure 1. Adding reagents simultaneously produced the higher-quality particles on the right

(Example 1).


additional cycle time needed for the rag layer to coalesce.Consider including an additional vessel to segregate therag layer for further settling. Sometimes a two-stage coun-tercurrent system can be employed where the rag layerwith one of the phases can be passed through a filter toremove solids as it is passed from one extractor to thenext. Also, there are a variety of coalescing filter designsto choose from (6). If you plan to use either a centrifugeor a coalescer, test its operation in the pilot plant.

Emulsions can sometimes be broken chemically. Considerchanging the solvent, although the options may be limited bythe reaction or extraction involved. Salt can be added to anaqueous phase to change the density or alter the surface prop-erties; this can sometimes be accomplished by recycling aportion of a purged brine stream. Another effective approachis to add a small amount of a surface-active agent to modifythe physical properties at the liquid interface.

Example 2: Changing the step sequence solves anemulsion problem through the pH/salt effect. A post-distil-lation slurry containing a crude organic product and a par-tially soluble HCl salt of an organic base was quenched inwater in a 2,000-gal vessel. The original procedure was todecant the organic product phase from the aqueous layer.Caustic was added to the remaining aqueous layer to neu-tralize the HCl salt, liberating the free base, which wasthen azeotropically distilled from the alkaline brine andrecycled. Upon scaleup, a fairly severe emulsion limitedcapacity and caused operational difficulty.

Excellent phase separation was achieved when theorganic product was decanted from the alkaline brine fol-lowing the base recovery operation. As a side benefit, oneof the impurities in the organic layer was hydrolyzed andremoved in the alkaline brine, which increased the purityof the product.

AgitationThe stirred tank reactor is the workhorse in many

chemical processes. Unfortunately, mixing (or agitation) ina stirred tank is often overlooked during the scale up ofnew processes. Successful scaleup involves three steps:classifying the mixing requirement, determining the mostcritical mechanism for scaleup, and then choosing thedesign of the mixing system (7).

The first question to consider is what kind of mixing isneeded. Is the goal to blend two liquids together, or tobring two or more different phases together such that achemical reaction involving mass transfer can occur at theinterface? Are solids being formed where the goal is tosuspend them gently without creating fines? Heat removalis an important consideration, particularly for highlyexothermic reactions. Consider the method of reactantincorporation, and whether feed location can have aneffect on side reactions; this can be important if competingreactions are very fast and can be affected by localizedconcentration gradients (8). The pumping direction createdby the agitator can be important, particularly in reactionsinvolving gas incorporation or removal.

Systems that are flow-dependent, such as the blendingof miscible liquids, can be scaled up based on impeller tipspeed. Some crystallizations can, too, provided the crystalsare suspended and moved through the region where thesupersaturation is created.

Reactions, crystallizations and extractions that are tur-bulence-dominated are often scaled up by keeping thepower per unit volume (P/V) constant. This is normally areasonable starting point for many new processes.

For reaction systems characterized by extremely fastkinetics with competing reactions, scaleup based on con-stant mixing time may be optimal, although this is typical-ly difficult and expensive. To illustrate this point, Table 1

presents a scale-down comparison of a1,000-gal plant reactor and the geometricallysimilar 2-gal reactor used in Example 1, bothfitted with dual pitched-blade turbines:

1. The agitation rate in the plant reactorwas 50 rpm (green). In testing the proposednew addition order, P/V was kept constant at0.58 (ft-lbf/s)/ft3. To achieve the P/V ratio inthe 2-gal lab reactor, a speed of 180 rpm wasnecessary. In this case, the results achievedin the lab and the plant were very similar.

2. However, if particles were sensitive toagitator tip speed, this could not be simulat-ed in the lab independent of P/V. At P/V =0.58 (ft-lbf/s)/ft3, the lab tip speed is 2.9 ft/s(red) only about half the tip speed of the


Table 1. Mixing scale-down example.

Plant Scale: 1,000 gal Laboratory Scale: 2 galMixing Tip Mixing Tip

Speed, Time, P/V, Speed, Time, P/V, Speed,rpm min (ft-lbf/s)/ft3 ft/s min (ft-lbf/s)/ft3 ft/s

30 3.9 0.12 3.7 3.2 0.003 0.550 2.3 0.58 6.1 1.9 0.01 0.875 1.6 1.95 9.1 1.3 0.04 1.2100 1.2 4.62 12.2 1.0 0.10 1.6140 0.8 12.67 17.1 0.7 0.27 2.3180 0.7 26.93 21.9 0.5 0.58 2.9250 0.5 72.16 30.5 0.4 1.57 4.1370 0.3 5.08 6.1


plant system (6.1 ft/s). To test at 6 ft/s, the lab reactorwould have to be run at 370 rpm, which would increaseP/V nearly tenfold, to 5.08 (ft-lbf/s)/ft3.

3. Finally, if a reaction were run at 180 rpm in the laband needed to be scaled up based on mixing time, toachieve mixing in 0.5 min, the plant agitation rate wouldneed to be 250 rpm (blue). This would increase P/V morethan a hundredfold (to 72.15 (ft-lbf/s)/ft3). This would bevery difficult to accomplish in a stirred tank reactor, soalternative contacting should be evaluated.

When scaling up agitation, pay attention to the impelleror turbine design, and to the tank baffling configuration.Many styles of impellers are tailored to the specific mix-ing requirement. Styles range from foil-type impellers thatcan deliver high axial flow with low shear, to high-shear,radial-flow, flat- or cupped-blade turbines designed for gasdispersion applications. Impeller physical dimensions,number and the power of the drive motor can be specified.

Keep in mind that the new process may be run in anexisting agitated vessel, so it is important to understandthe type of system available and its limitations. Forinstance, if the equipment is glass-lined steel, the reactorwill usually have a large-diameter, crow-foot agitatorand an h-type or beaver-tail baffle that can createturbulence but not axial flow. In a metal vessel, bafflescan be welded close to the reactor wall, which willchange the flow direction produced by the agitator fromradial to axial flow.

Process development research should test very high andvery low agitation rates to determine sensitivity to mixing. Ifthe results are mixing-sensitive, consult with a mixing expertand consider testing in a larger vessel. Finally, consider othersources of turbulence and mixing, such as would be encoun-tered in a recirculation loop or other equipment.

Example 3: Shear-induced phase inversion produced ahigh-viscosity emulsion. A product isolation processrequired extraction of the solute from an organic solventusing dilute aqueous acid. In normal operation, the water-in-oil dispersion of the two similar-density liquids was fedto a stacked-disc centrifuge to separate the phases (Figure2). Upon scaleup, an occasional high-viscosity, pudding-like emulsion formed, which choked off the centrifuge andseverely limited plant throughput.

It was determined that the emulsion was caused by aphase inversion phenomenon. The aqueous phase becamethe continuous phase, which was surprising because theaqueous-to-organic-phase ratio was very low (0.16 to 1).Phase inversions often occurred during centrifuge restartsor upsets. Lab studies showed phase inversions resultedwhen high shear was introduced in the quiescent aqueousphase that resulted during upsets.

Analysis of the plant operation revealed that the shear-inducing turbine design in the centrifuge feed tank (reusedequipment), the piping configuration, and the operatingprocedures all contributed to the problem. No phase inver-sions could be created at phase ratios < 0.14, or when asmall amount of a specific surfactant was added to the sys-tem. Several subsequent modifications to the process pre-vented phase inversions from occurring in the plant.

Heat management considerationsA common scaleup axiom is Everything takes longer

and runs hotter in the plant. The key scaleup considera-tion is that the volume-to-surface-area ratio increases inproportion to vessel diameter. A 1,000-gal reactor has 10%of the relative heat-removal surface area of a 1-gal reactor.

It is essential to understand the heat involved in theprocess the heat of reaction and heats of vaporizationfor all desired processing. An accelerating rate calorimeteris a useful tool for determining the point of onset, poten-tial rate and magnitude of energy release from unplannedreactions or thermal runaways.

Often, a highly exothermic reaction needs to be scaledup. Typically, adding one of the reactants continuously cancontrol the exotherm. Be sure to starve the reaction anddont build up potential energy by adding the reactant toofast, which could lead to a thermal runaway situation. Adynamic heat balance can confirm that the reaction is pro-ceeding normally before all of the reactant is added. Thisis especially important if a minor component or catalyst ismistakenly omitted or if agitation stops.

Determine the heat removal capability of equipment tobe used in the plant. Be aware that the heat-transfer coef-ficient for a glass-lined steel reactor may be 50% or lessthan that of an alloy vessel. If an existing vessel is to beused, the jacket may have some fouling, which will limitheat transfer. This can usually be remedied by cleaningthe jacket periodically and by using clean or treated heat-transfer fluid.

Raffinate

Extract

Stacked Disc Centrifugal Separator

1% H2SO4 (0.16 of feed)Feed

4,000-gal Vessel withtwo Radial

Flow Turbines

Figure 2. The stacked-disc centrifuge in this product extraction processoccasionally was choked by a high-viscosity emulsion (Example 3).


Perform heat balance calculations to determine howlong heat removal steps (i.e., exothermic reactions or dis-tillation steps) will take in the plant, then simulate these inthe lab. If there are no adverse effects on yield, quality orcycle time, then you should be able to remove or add heatdirectly through the jacket.

If greater heat removal capability is required, thiscan be accomplished by adding a heat exchanger in arecirculation loop, although this can introduce otherproblems. An option may be to remove heat via areflux condenser, sometimes by the addition of a low-boiling liquid.

Distillation considerationsBatch distillation is usually a good choice for relatively

low volume production. It integrates well with other batchunit operations, is flexible for making multiple distillationcuts, and handles mixtures with solids and variable feedcomposition. Quite often, vacuum distillation is needed toachieve reduced temperature for heat-sensitive applica-tions. If a distillation column is used, lower-pressure oper-ation will require a larger-diameter column to achievecomparable rates. As the column diameter is increased, theheight of a theoretical stage may also increase, so a com-promise must be struck.

Modeling the distillation is recommended. It is alsoprudent to conduct the lab distillation at the anticipatedtime/temperature profile in the plant, using a columndesigned to achieve the desired separation. Be awarethat even if the time is simulated in the lab, the walltemperature in the plant vessel will be higher. This canbe tested by limiting the heat-transfer area in a special-ly designed lab reactor to mimic the area/volume ratioin the plant vessel. If the heat history is excessive, con-sider alternative separation technology, such as short-path or multi-pass continuous distilla-tion, solvent or melt crystallization, orsolvent extraction.

Example 4: Side reaction is four timeshigher in the plant due to heat history. Ahighly exothermic, semi-batch reactionwas scaled up from a 1-gal lab vessel toa 750-gal plant reactor. Yield loss to adimer byproduct was three to four timeshigher in the plant than in the lab. It wassuspected that the cause was from run-ning the reaction about 510C hotter inthe plant in order to meet cycle timerequirements.

The chemistry involved two competingreactions in series:

Desired: A + B C fast, product formation

Competing: A + C D slow, dimer formation

During process development studies, time and tempera-ture were tested independently, but worst-case plant condi-tions were not studied. In all tests, dimer levels were con-sistently less than 1%.

In a follow-up lab study, the cause of the higher dimerlevel was confirmed, and temperature was found to be themore important variable. When the reaction was conductedat 05C for 9 h, which would be achievable in the plant,the dimer level was < 1%. Furthermore, when the concen-tration of Reactant A was kept low by metered addition, thedimer level was very low (< 0.5%), even at 20C.

Trace chemistryConsider all sources of impurities, including raw mate-

rials, side reactions and accumulation in recycle loops.Then determine the fate of all impurities in the process.Modeling impurity buildup in recycle loops can also bevaluable. If the reaction conversion or the amount ofexcess reactant(s) can vary from batch to batch, evaluatethe impact of such variation on the impurity spectrum.Processes with recovery and recycle loops should includeprovisions for purging impurities. Finally, consider theeffects of impurities on product quality.

In planning process development research, evaluatecommercial-grade raw materials. Analyze for tracechemistry in all process streams, including vents, as thiscan be a source of reactive chemistry concern. Spike labruns with high levels of impurities to determine therobustness of the process. Run up to 10 cycles in the labusing recycle streams to identify potential problems atsteady state.


Cake Depth, cm

Projected Rate due to loss in cake permeability

based on 16 cm data

Extrapolated Performance based on 10 cm data fornormal cake resistanceI

nvers

e D

rain

Rat

e, 1/

(g/s-c

m2

0.0

0.5

1.0

1.5

2.0

2.5

3.0

0 5 10 15 20 25

Figure 3. Cake resistance increases sharply at depths greater than 15 cm (Example 5).


Example 5: Feed impurity causeda filtration problem. A semi-batchcrystallization process was scaled upfrom a 1.5-L lab crystallizer to a2,000-gal vessel with a 4-m2 filter.Upon scaleup, excellent productcrystals, very similar to those pro-duced in the lab, were formed.

The filtration rate, however, wasvery slow, with some batches requir-ing up to three days to complete. Inaddition, the plant experienced poorcake washing and slow drying. Slurrysamples from the plant were filteredin the lab to confirm the problem.

For normal filtrations, a linearrelationship exists between theinverse of the filtration rate and thecake resistance or thickness. The datain Figure 3 show a linear relationshipat cake depths below 10 cm, but asteep increase in cake resistanceabove 15 cm. It was determined thata floc-like solid clogged the voids inthe cake, decreasing permeability.The floc was traced to an impurity ina raw material, which was present atroughly twice the level tested in thelab during process development. Also, the maximum cakedepth tested in the lab was only 10 cm, while the beddepth in the plant was 25 cm.

To solve the problem, the plant shut off the agitator andallowed the crystals to settle. The mother liquor containingthe floc was decanted to waste treatment, and the productcrystals were diluted with wash water and fed to the filter,resulting in cycle times less than 24 h.

Recommended approaches for process development and scaleup

The single most important thing you can do in theprocess development phase to ensure a successful scaleupis to promote and ensure early-stage, ongoing teamworkbetween chemists and engineers. Unfortunately, engineersare often brought in too late and chemists are pulled fromdevelopment projects too early. Management should pro-vide incentives to foster this desirable, collaborative envi-ronment from the outset of the project.

A holistic methodology that considers cost of manufac-ture, capital, complexity, robustness, environmental,health, safety and scaleability issues should be used toevaluate possible process routes.

Model, simulate and rigorously test expected plant con-ditions, particularly materials of construction, agitation,heat removal and separations.

Acquire and test commercial-grade raw materials. Perform insult studies to test process robustness.

Brainstorm with your manufacturing colleagues to deviseinsult scenarios. Insult variables include time, temperature,pH, agitation, reagent quality and stoichiometry, and mate-rials of construction.

Establish success parameters for your scaleup, such asthose in Table 2. Select two or three performance metricsper unit operation, such as yield or cycle time. Once stableoperation is achieved, compare the actual values with labor expected results to identify gaps. These may becomethe focus of follow-up research and optimization.

Tools for process development and scaleupUse geometrically scaled lab reactors and separation

systems made from the materials of construction to beused in the plant. Computer control and data collectioncapabilities are useful.

Use in situ analysis to gain as much information fromyour new process as possible.

Table 2. Example of success parameters.

NeedsUnits Work Excellent Actual

Reactant DryingEvaporation Time h >18 12 1 4 12 4 36 48Wash Rate lb/lb >4 0.5


Understand the energy of the system for both plannedand unplanned chemistries. Use calorimeters to obtain heatsof reaction. Perform other reactive chemicals testing, such asdifferential scanning calorimetry (DSC), accelerated ratecalorimetry (ARC), and dust explosion testing.

Use computer models to evaluate expected plant conditions.

Closing thoughtsMany new chemical processes, particularly those involv-

ing batch operations, can be scaled up directly from thebench to the plant. However, not all processes should bescaled up without pilot plant demonstration. As a processdevelopment engineer or chemist, you need to evaluate therisks and benefits of each scaleup strategy. Be aware of andtest scale-sensitive parameters, including solids operations,multi-phase systems, agitation, heat transfer and history, andthe effects of trace chemistry. Develop the process and per-form lab testing with the scaleup in mind. Liberally consultwith subject matter experts. Finally, plan for a successfulstart up and evaluate the results. CEP


RONALD B. LENG is currently a process development leader in theChemical Sciences Dept. of The Dow Chemical Co. (1710 Building,Midland, MI 48674; Phone: (989) 636-6158; E-mail: [email protected]).During his 23-year career, he has held a variety of positions both inresearch and development and manufacturing. His chief interests lie inbridging the gap from the lab to the plant, and he has worked on anumber of process development teams to bring new processes foragricultural chemical products to realization. Particular interests includeunderstanding key scaleup fundamentals and their practical applicationto the plant environment. He has a BS in chemical engineering from theMichigan Technological Univ.

Literature Cited1. Bisio, A., and R. L. Kabel, Scaleup of Chemical Process,

Wiley, Hoboken, NJ, p. 3 (1985).2. Anderson, N. G., Practical Process Research and

Development, Academic Press, San Diego, CA (2000).3. Myerson, A. S., Handbook of Industrial Crystallization,

Butterworth-Heinemann, Newton, MA, pp. 1519 (1993).4. Perry, R. H. and D. W. Green, eds., Perrys Chemical

Engineers Handbook, 6th ed., Chapter 19, pp. 65103,McGraw-Hill, New York, NY (1984).

5. Purchas, D. B., ed., Solid-Liquid Separation EquipmentScaleup, Uplands Press, London, pp. 493553 (1977).

6. Osmonics, Inc., Liquid/Liquid and Gas/Liquid CoalescingHandbook, Ninnetoka, MN (1991).

7. Paul, E. L., et al, eds., Handbook of Industrial Mixing,Wiley, Hoboken, NJ (2004).

8. Fasano, J. B., and W. R. Penney, Cut ReactionByproducts by Proper Feed Blending, Chem. Eng. Progress,87 (12), pp. 4652 (Dec. 1991).

Further Reading

Sharnatt, P. N., Pilot Plants and Scale-up of ChemicalProcesses, Hoyle, W., ed., Royal Society of Chemistry,Cambridge, UK, pp. 1321, 130, 655690 (1997).

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